We intend investigating at the molecular level the mechanisms by which adeno-associated satellite viruses interfere with the replication and potential oncogenesis of their helper adeno-viruses and herpes viruses. We will use conditionally-defective helper viruses, namely temperature-sensitive mutants of human adenovirus type 31 and herpes simplex virus known to be defective in viral DNA synthesis and their virus-specific functions. Complementation studies with these mutants will simplify dissection of the defective satellite replication cycle. Satellite viruses are defective at both the maturation and replication steps. We will use fluorescein-labeled antibodies, complement fixation assays and electron microscopy to study the satellite maturation step in tissue cultures preinfected with herpes virus and satellite viruses and later challenged with adenovirus. In experiments to study the replication of satellite virus DNA we will use DNA-negative herpes simplex mutants as helpers and biophysical techniques based on ultracentrifugation of viral components radio-actively labeled in vitro. We have already used these latter techniques in a preliminary investigation of satellite DNA using adenovirus helpers. These studies should be of considerable importance in understanding the mechanisms for abrogation of adenovirus (and possibly herpes virus)-derived tumors by satellite virus which we have recently described. BIBLIOGRAPHIC REFERENCES: Mayor, H. D., and Gorman, C. Growth of adeno-associated satellite virus under conditions of arginine deprivation. Virology 66, 25-36, 1975. Mayor, H. D., Drake, S., and Jordan, L. The replication of adeno-associated satellite virus: the three-component system, satellite, herpesvirus and adenovirus. J. Ultrastructure Research 52, 52-63, 1975.